Fourier Transform Mass Spectrometry for Proteomics and Genomics: Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS) instruments are relatively new to proteomics and genomics research. FTICR/MS rapidly provides highly accurate mass determinations of peptides derived from protease digests of intact proteins. Thus, FTICR-MS systems provide unparalleled capabilities for rapid fingerprinting of known proteins as well as the characterization of new proteins. They can also be used for the unequivocal characterization of covalently modified DNA. Thus, such instruments are essential for state-of-the-art of research in the area of proteomics research when only trace amounts of material are available. The Thermo Finnigan system (LTQ FT) can utilize a variety of ionization techniques: ESI, APCI, APPI or MALDI. Maintenance of the API source, as well as switching between AP ionization methods, is vent-free. Ions are transferred by octapole and "square" quadrupole lenses into a novel ion trap. The linear ion trap is a fully operational mass spectrometer, which can store, isolate, and fragment ions and then send them either to the ICR cell via axial ion ejection for further analysis or to an off-axis SEM detector. The linear ion trap is a unique ion preparation and injection system for FTICR-MS because it has much greater ion storage capacity than conventional 3D ion trap devices. Ions from the ion trap are transferred as discrete bundles into the ICR cell, via octapole ion guides. These octapole ion guides are designed to enable very efficient differential pumping between the ion trap and the ICR cell. The FTICR analyzer is built around an actively shielded superconducting magnet with a field strength of 7 Tesla. The investigators involved in this proposal have research programs that represent four major research areas within the University of Pennsylvania. These programs are highly interactive. Dr. Blair as Director of the Center for Cancer Pharmacology and Scientific Director of the Genomics Institute Proteomics Resource is a member the Cancer Center, the Center for Experimental Therapeutics, and the Institute for Medicine and Engineering. Dr. FitzGerald as Director of the Center for Experimental Therapeutics and a member of the Institute for Medicine and Engineering has extensive interactions with Dr. Davies, Director of the Institute for Medicine and Engineering and Dr. Rader, Director, Lipid Clinics; Assistant Director, General Clinical Research Center through an existing program project grant and a SCOR grant. Three additional investigators from these research programs (Drs. Eberwine, Ischiropoulos, and Roos) will require access to the instrument on a more limited basis. The proposed research on the two major degenerative disease of aging, cancer and cardiovascular disease, will involve a highly interactive approach. This will permit advances made by one investigator to be readily incorporated into research of the other investigators. Thus, while each investigator's research proposal stands alone in scientific value and integrity, the added value of this combined proposal is substantial.